ArticleCirculation. Cardiovascular genetics2011
Biophysical and molecular characterization of a novel de novo KCNJ2 mutation associated with Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry.
Article in Circulation. Cardiovascular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 34 citations in OpenAlex.
- Kir2.1 mutations differentially increase the risk of flecainide proarrhythmia in Andersen Tawil Syndrome.medRxiv : the preprint server for health sciences · 2024Article
- The network of cardiac KNaunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Inward rectifier potassium (Kir) channels in the retina: living our vision.American journal of physiology. Cell physiology · 2022Review
- Pediatric Catecholaminergic Polymorphic Ventricular Tachycardia: A Translational Perspective for the Clinician-Scientist.International journal of molecular sciences · 2021Review
- Characterization of Loss-Of-FunctionFrontiers in genetics · 2021Article
- Genetic Loss ofCirculation. Arrhythmia and electrophysiology · 2020Article
- Multivariate analysis of TU wave complex on electrocardiogram in Andersen-Tawil syndrome with KCNJ2 mutations.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2020Article
- Andersen-Tawil Syndrome Is Associated With Impaired PIPFrontiers in pharmacology · 2020Article
- Asymptomatic ventricular tachycardia: diagnostic pitfalls of Andersen-Tawil syndrome-a case report.European heart journal. Case reports · 2018Article
- Kir2.1 & NaCirculation research · 2018Article
- Electrophysiologic effects of the IK1 inhibitor PA-6 are modulated by extracellular potassium in isolated guinea pig hearts.Physiological reports · 2017Article
- Cardiac Ion Channel Regulation in Obesity and the Metabolic Syndrome: Relevance to Long QT Syndrome and Atrial Fibrillation.Frontiers in physiology · 2017Review
- Genomic-based diagnosis of arrhythmia disease in a personalized medicine era.Expert review of precision medicine and drug development · 2016Article
- Negative autopsy and sudden cardiac death.International journal of legal medicine · 2014Review
- KCNJ2 mutation causes an adrenergic-dependent rectification abnormality with calcium sensitivity and ventricular arrhythmia.Heart rhythm · 2014Article
- Gene mutations in cardiac arrhythmias: a review of recent evidence in ion channelopathies.The application of clinical genetics · 2013Article
- Novel insights into the pathomechanisms of skeletal muscle channelopathies.Current neurology and neuroscience reports · 2012Review
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8 authors at 1 institution in 1 country.
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Abstract
backgroundMutations in KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1 (IK1 or IKir2.1), have been identified in Andersen-Tawil syndrome. Andersen-Tawil syndrome is a multisystem inherited disease exhibiting periodic paralysis, cardiac arrhythmias, and dysmorphic features at times mimicking catecholaminergic polymorphic ventricular tachycardia. METHODS AND
resultsOur proband displayed dysmorphic features including micrognathia, clinodactyly, and syndactyly and exhibited multiform extrasystoles and bidirectional ventricular tachycardia both at rest and during exercise testing. The patient's symptoms continued after administration of nadolol but subsided after treatment with flecainide. Molecular genetic screening revealed a novel heterozygous mutation (c.779G>C/p.R260P) in KCNJ2. Whole-cell patch-clamp studies conducted in TSA201 cells transfected with wild-type human KCNJ2 cDNA (WT-KCNJ2) yielded robust IKir2.1 but no measurable current in cells expressing the R260P mutant. Coexpression of WT and R260P-KCNJ2 (heterozygous expression) yielded a markedly reduced inward IKir2.1 compared with WT alone (-36.5±9.8 pA/pF versus -143.5±11.4 pA/pF, n=8 for both, P<0.001, respectively, at -90 mV), indicating a strong dominant negative effect of the mutant. The outward component of IKir2.1 measured at -50 mV was also markedly reduced with the heterozygous expression versus WT (0.52±5.5 pA/pF versus 23.4±6.7 pA/pF, n=8 for both, P<0.001, respectively). Immunocytochemical analysis indicates that impaired trafficking of R260P-KCNJ2 channels.
conclusionsWe report a novel de novo KCNJ2 mutation associated with classic phenotypic features of Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia mimicry. The R260P mutation produces a strong dominant negative effect leading to marked suppression of IK1 secondary to a trafficking defect.
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